title: Dose finding study of erlotinib combined to capecitabine and irinotecan in pretreated advanced colorectal cancer patients.
abstract: OBJECTIVE
  This study evaluated the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine in pre-treated metastatic colorectal cancer patients.
  
  
  METHODS
  Five dose level combinations with irinotecan (from 180 to 240 mg/m(2), day 1, q21), capecitabine (1,500-2,000 mg/m(2) per day, days 2-15, q21) and erlotinib (50-150 mg per day, continuously) were planned. Patients were enrolled in cohorts of three, and evaluated for first cycle acute toxicity.
  
  
  RESULTS
  Twenty-one patients were treated. In the first cohort, no DLT was reported, in the second: one DLT (G4 neutropenic fever associated with G3 cutaneous rash and mucositis); in the third dose level: two DLT (G3 diarrhea and G4 neutropenic fever). To confirm these results, other six patients were additionally included and no DLT was observed.
  
  
  CONCLUSIONS
  The results documented that erlotinib at the dose of 100 mg per day, irinotecan 180 mg/m(2) and capecitabine 1,500 mg/m(2) per day for 14 days has an acceptable safety profile and appears suitable for further phase II studies.
authors.affiliation: Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. emilio.bajetta@istitutotumori.mi.it
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: Roberto
authors.initials: R
authors.lastname: Buzzoni
authors.forename: Erminia
authors.initials: E
authors.lastname: Ferrario
authors.forename: Katia F
authors.initials: KF
authors.lastname: Dotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Roberto
authors.initials: R
authors.lastname: Bajetta
authors.forename: Arpine
authors.initials: A
authors.lastname: Gevorgyan
authors.forename: Paola
authors.initials: P
authors.lastname: Venturino
authors.forename: Margherita
authors.initials: M
authors.lastname: Galassi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology; D000069347:Erlotinib Hydrochloride; D005260:Female; D005334:Fever / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011799:Quinazolines / Q000008:administration & dosage
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D002166:Camptothecin